Comparative tumor-initiating activity of methylene-bridged and bay-region methylated derivatives of benz[a]anthracene and chrysene

Abstract

Polycyclic aromatic hydrocarbons (PAHs) with a methylene-bridge spanning the bay region are often detected in higher concentrations in the environment than PAHs which have a bay-region methyl substituent. The tumor-initiating activity of methylene-bridged bay-region derivatives of chrysene and benz[a]anthracene was evaluated on the skin of female CD-1 mice. 4,5-Methylenechrysene elicited twice as many tumors as chrysene at each of the doses tested. At total initiation doses of 1.5, 0.5 and 0.15 mumol/mouse 4,5-methylenechrysene gave rise to 8.5, 6.8 and 1.1 tumors/animal respectively. There was a 100% incidence of tumor-bearing mice at the two higher doses and a 65% incidence at the lowest dose. This methylene-bridged hydrocarbon was less tumorigenic than 5-methylchrysene at each dose tested. Animals treated with 1,12-methylenebenz[a]anthracene developed 7.6, 4.9 and 1.6 tumors/animal at total initiating doses of 4.0, 2.0 and 0.5 mumol/mouse. The incidence of tumor-bearing mice was 90% at the higher doses and 75% at the lowest dose tested. 12-Methylbenz[a]anthracene was more tumorigenic than the methylene-bridged derivative at each dose. The keto-derivative of 1,12-methylenebenz[a]anthracene did not display significant (P greater than 0.05) tumor-initiating activity at these dose levels. Results from these bioassays indicate that methylene-bridged bay-region derivatives of chrysene and benz[a]anthracene contribute to the overall genotoxicity of environmentally occurring PAHs.